Current Research on the δ-Opioid Receptor: From Neuroprotection Against Hypoxia/Ischemia to Broad Neural Functions

Xia, Ying

doi:10.1007/978-3-319-25495-1_1

Cited by 5 publications

(12 citation statements)

References 180 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we have demonstrated that the δ-opioid receptor (DOR) is protective against anoxic/ischemic injury in the brain, and that its underlying mechanisms involve the regulation of ionic homeostasis and antioxidative capacity [17][18][19][20][21]. There are also other studies showing that DOR agonists can prolong survival of peripheral organs, such as the lungs, heart, liver, and kidney, and that DOR activation is protective against hypoxic/ischemic injury in the heart [22,23].…”

Section: Introductionmentioning

confidence: 99%

δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

Zhi

Li²,

Shao³

et al. 2016

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background: Hypoxic/ischemic injury to the heart is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ischemic events, and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering miRNA expression in the heart under hypoxic conditions. The present study aimed to test our hypothesis. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O₂) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected from TaqMan low-density array (TLDA) data and were further analyzed by quantitative real-time PCR. Results: We found that: 1) hypoxia alters the miRNA expression profiles depending on the hypoxic duration; 2) DOR activation shifts miRNA expression profiles in normoxic conditions and upregulates miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, and miR-338; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression and increases the levels of miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, miR-141, miR-200b, and miR-324-3p. For example, miR-196c-5p decreased by 50% while miR-135a-5p increased 2.9 fold after 10 days under hypoxic conditions. Moreover, DOR activation further strengthened the hypoxia-induced increase of the levels of miR-7a-5p. When DOR was activated using UFP-512, the level of miR-107-3p significantly increased 1 day after the administration of UFP-512, but gradually decreased back to normal under normoxia. Conclusion: Hypoxia significantly modifies the miRNA profile in the heart, which can be mimicked or modified by DOR activation. Defining the targeted pathways that regulate the diverse cellular and molecular functions of miRNAs may provide new insights into potential therapies for hypoxic/ischemic injury of the heart.

show abstract

Section: Introductionmentioning

confidence: 99%

δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

Zhi

Li²,

Shao³

et al. 2016

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

Section: δ-Opioid Receptors In Neurons Versus Microgliamentioning

confidence: 99%

“…DOR is widely distributed in the CNS with a high expression level in the cortex, caudate, putamen, and amygdala [ 8 , 70 , 71 ]. Our previous studies have well demonstrated that DOR activation protects cells against various injuries: hypoxic/ischemic, parkinsonian, and Alzheimer’s [ 8 , 13 , 14 , 16 , 17 ]. Mechanistic studies showed that DOR-mediated neuroprotection is mainly through stabilizing ionic homeostasis, inhibiting excitatory transmitter release, and attenuating neurotransmitter disturbance in acute phase of stress, while DOR presents anti-oxidant capacity, inhibits inflammation, and regulates several signaling pathways: PI3K/Akt, extracellular signal-regulated kinase (ERK) and BDNF-TκkB to attenuate CNS injury during prolonged stress [ 11 , 72 - 74 ].…”

Section: δ-Opioid Receptors In Neurons Versus Microgliamentioning

confidence: 99%

“…Erbs et al reported that DOR is mainly present in GABAergic neurons, participating in the dynamic regulation of hippocampal activities [ 85 ]. Ma et al [ 73 ] examined the changes in DOR expression in primary cultured rat cortical neurons and found that mild hypoxia caused an increase in DOR mRNA and protein, while severe hypoxia significantly decreased DOR expression with serious cell injury, suggesting DOR expression is sensitively influenced by environmental stresses [ 8 , 73 , 74 ].…”

Section: δ-Opioid Receptors In Neurons Versus Microgliamentioning

confidence: 99%

“…Opioid receptors belong to a G protein-coupled receptors (GPCRs) family with three key members: μ, δ, and κ opioid receptors (MOR, DOR, KOR) [ 8 ]. Although the most prominent tag of these opioid receptors is their modulation of pain signaling, the analgesic effects are primarily through activation of MOR [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

δ-opioid Receptor, Microglia and Neuroinflammation

Xu¹,

Chen²,

Zhi³

et al. 2023

Aging and disease

Self Cite

View full text Add to dashboard Cite

Neuroinflammation underlies the pathophysiology of multiple age-related neurological disorders. Microglia, the resident immune cells of the central nervous system, are critically involved in neuroinflammatory regulation and neural survival. Modulating microglial activation is thus a promising approach to alleviate neuronal injury. Our serial studies have revealed a neuroprotective role of the δ-opioid receptor (DOR) in several acute and chronic cerebral injuries by regulating neuroinflammation and cellular oxidative stress. More recently, we found an endogenous mechanism for the inhibition of neuroinflammation is closely related to DOR’s modulation of microglia. Our recent studies showed that DOR activation could strongly protect neurons from hypoxia- and lipopolysaccharide (LPS)-induced injury by inhibiting microglial pro-inflammatory transformation, while knocking-down DOR or restraining DOR activity promoted microglia activation and the relevant inflammatory events with an aggravation of cell injury. This novel finding highlights a therapeutic potential of DOR in numerous age-related neurological disorders through the modulation of neuroinflammation by targeting microglia. This review summarized the current data regarding the role of microglia in neuroinflammation, oxidative stress, and age-related neurological diseases focusing on the pharmacological effects and signaling transduction of DOR in microglia.

show abstract

Factors Influencing Acupuncture Research

Wang¹,

Xia

2019

Translational Acupuncture Research

View full text Add to dashboard Cite

Current Research on the δ-Opioid Receptor: From Neuroprotection Against Hypoxia/Ischemia to Broad Neural Functions

Cited by 5 publications

References 180 publications

δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

δ-opioid Receptor, Microglia and Neuroinflammation

Factors Influencing Acupuncture Research

Contact Info

Product

Resources

About